T cells with increased immunosuppression resistance
This invention relates to the treatment of cancer in an individual by administration of a population of modified T cells that express a recombinant cAMP phosphodiesterase (PDE) or a fragment thereof and an antigen receptor which binds specifically to cancer cells in the individual. Populations of modified T cells and methods of producing populations of modified T cells are provided, along with pharmaceutical compositions and methods of treatment.
1. A method of treating cancer comprising administering to an individual with cancer a population of modified T cells which express:
(i) an antigen receptor which binds specifically to tumour antigens on cancer cells; and
(ii) a cAMP phosphodiesterase 7A (PDE7A) or a cAMP phosphodiesterase 4C (PDE4C) or a fragment thereof, wherein said cells comprise a heterologous nucleic acid encoding the cAMP phosphodiesterase 7A (PDE7A) or the cAMP phosphodiesterase 4C (PDE4C).
2. A method according to claim 1 wherein the cancer is characterized by the presence of one or more cancer cells which bind to said antigen receptor.
3. A method according to claim 1 wherein the antigen receptor binds specifically to a major histocompatibility complex (MHC) displaying a peptide fragment of a tumour antigen expressed by the cancer cells.
4. A method according to claim 3 wherein the tumour antigen is NY-ESO-1, MAGE-A4 or MAGE-A10.
5. A method according to claim 1 wherein the cancer cells are melanoma cells.